This project will evaluate the effects of pharmacological agents which may result in improved treatments for opioid dependence and for opioid detoxification, and will utilize the clinical resources of a methadone maintenance clinic to develop and utilize human experimental procedures for assessing the abuse liability of drugs in a population of experienced abusers. Within an outpatient opiate addiction treatment/research clinic four sets of studies will be undertaken. One series of experiments will evaluate the utility of the mixed opioid agonist-antagonist buprenorphine as a treatment for narcotic addiction. Buprenorphine will be evaluated for its therapeutic efficacy in maintenance and detoxification treatment, and its pharmacological profile in terms of abstinence precipitation or substitution for methadone will be evaluated in both acute and chronic dosing regimens and at low and high methadone maintenance dose levels. Second, a series of methadone detoxification studies will evaluate and compare the effects and efficacies of a variety of pharmacological adjuncts often used or recommended as aids to detoxification -- buprenorphine, clonidine, lofexidine, diazepam, doxepin, flurazepam and secobarbital. In a third set of studies the acute effects and discriminability of various benzodizaepine minor tranquilizers will be assessed in methadone maintenance patients with histories of sedative/tranquilizer abuse, and a behavioral choice procedure will be used to assess and compare the relative abuse liabilities of these different compounds. A fourth series of studies will assess effects of intravenous opioids; the effects upon opioid sensitivity and detectability of various pharmacological treatments -- methadone maintenance, naltrexone maintenance, buprenorphine maintenance -- will be assessed, and a within-subject drug discrimination procedure will be developed and used to assess the relative discriminative properties and effects of various narcotic agonists, antagonists and mixed agonist-antagonists.